It is proposed to examine the cellular and molecular mechanisms by which vascularized organ allografts are rejected or accepted. A state of specific unresponsiveness towards transplant antigens in rats will be elucidated. The subpopulation(s) of suppressor cells will be identified with monoclonal antibodies. Their specific role will be explored in the adoptive transfer assay and in novel assays. Their reactivity against alloantigen or idiotype, as well as the role of MCH antigen release in the specifically unresponsiveness state will be examined. New techniques to illuminate the suppressor response will include culture and cloning of the suppressor cells, in vitro induction of cells that either induce or effect the response, and assay and mRNA analysis of lymphokines that facilitate the unresponsive state. To determine the variable induction of unresponsiveness among various strains, the rejection, reaction and suppressor cells from such strains will be compared using in vivo and in vitro systems. Better characterization of suppressor mechanisms should permit (1) the development of in vitro assays to detect unresponsiveness in transplanted patients, thereby minimizing the need for non- specific immunosuppression; and (2) Strategies to induce suppressor responses in clinical transplantation.